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Effective radical cure of Plasmodium vivax malaria is essential for malaria elimination in Brazil. P. vivax radical cure requires administration of a schizonticide, such as chloroquine, plus an 8-aminoquinoline. However, 8-aminoquinolines cause hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, requiring prior screening to exclude those at risk. Brazil is pioneering the implementation of tafenoquine, a single-dose 8-aminoquinoline indicated for P. vivax patients with >70% of normal G6PD activity. Tafenoquine implementation in Manaus and Porto Velho, two municipalities located in the western Brazilian Amazon, included comprehensive training of healthcare professionals (HCPs) on point-of-care quantitative G6PD testing and a new treatment algorithm for P. vivax radical cure incorporating tafenoquine. Training was initially provided to higher-level facilities (phase one) and later adapted for primary care units (phase two). This study analyzed HCP experiences during training and implementation and identified barriers and facilitators. In-depth interviews and focus discussion groups were conducted 30 days after each training for a purposive random sample of 115 HCPs. Thematic analysis was employed using MAXQDA software, analyzing data through inductive and deductive coding. Analysis showed that following the initial training for higher-level facilities, some HCPs did not feel confident performing quantitative G6PD testing and prescribing the tafenoquine regimen. Modifications to the training in phase two resulted in an improvement in understanding the implementation process of the G6PD test and tafenoquine, as well as in the knowledge acquired by HCPs. Additionally, knowledge gaps were addressed through in situ training, peer communication via a messaging app, and educational materials. Training supported effective deployment of the new tools in Manaus and Porto Velho and increased awareness of the need for pharmacovigilance. A training approach for nationwide implementation of these tools was devised. Implementing quantitative G6PD testing and tafenoquine represents a significant shift in P. vivax malaria case management. Consistent engagement with HCPs is needed to overcome challenges in fully integrating these tools within the Brazilian health system.

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INTRODUCTION: Left bundle branch block (LBBB) disrupts the electrical activation of the left ventricle, potentially impairing its systolic function, leading to LBBB-induced cardiomyopathy. This study examined cardiopulmonary exercise test (CPET) variables in patients with and without LBBB and assessed the longitudinal development of left ventricular ejection fraction (LVEF). METHOD: An observational, comparative clinical study was executed in two stages at a private hospital in Brazil. The sample consisted of 27 individuals: 11 with LBBB and 16 without LBBB, all with preserved LVEF (>50%) and without confirmed ischemia. CPET variables were assessed, and after 4 years, participants had a transthoracic echocardiogram for LVEF re-evaluation. Groups were compared using the t test or the χ2 test. Multivariate analysis of covariance determined effect magnitude. RESULTS: Patients with LBBB demonstrated significant differences in CPET variables, particularly in predicted peak V˙O2, predicted peak PO2, V˙E/V˙CO2 slope, and T ½ V˙O2. They also exhibited a more significant decline in LVEF over a 4-year span compared to the patients without LBBB. Although initial preservation of LVEF, changes in contractile patterns due to LBBB interfered with its systolic function, suggesting early ventricular dysfunction indicated by a reduction in LVEF and an increase in the V˙E/V˙CO2 slope. Despite differences in cardiopulmonary function and changes in LVEF over time between patients with and without LBBB, the effect size was considered mild to moderate. CONCLUSIONS: LBBB patients with initially preserved LVEF displayed reduced exercise tolerance and a decrease in LVEF over time, emphasizing the need for vigilant monitoring and early intervention in these patients.

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BACKGROUND: Malaria is one of the leading causes of morbidity worldwide, and patient adherence to prescribed antimalarials is essential for effective treatment. METHODS: This cross-sectional study, with in-depth telephone interviews, analyzed participants' perceptions of short message service (SMS) in adherence to treatment. RESULTS: Five thematic categories emerged: decreased forgetfulness, the novelty of the tool, easy-to-understand language, the impact of SMS messages during treatment, and suggestions for improvement and complaints. CONCLUSIONS: SMS could assist patients in adhering to prescribed antimalarials.

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In the Brazilian Amazon, deaths and disabilities from snakebite envenomations (SBEs) are a major and neglected problem for the indigenous population. However, minimal research has been conducted on how indigenous peoples access and utilize the health system for snakebite treatment. A qualitative study was conducted to understand the experiences of health care professionals (HCPs) who provide biomedical care to indigenous peoples with SBEs in the Brazilian Amazon. Focus group discussions (FGDs) were carried out in the context of a three-day training session for HCPs who work for the Indigenous Health Care Subsystem. A total of 56 HCPs participated, 27 in Boa Vista and 29 in Manaus. Thematic analysis resulted in three key findings: Indigenous peoples are amenable to receiving antivenom but not to leaving their villages for hospitals; HCPs require antivenom and additional resources to improve patient care; and HCPs strongly recommend a joint, bicultural approach to SBE treatment. Decentralizing antivenom to local health units addresses the central barriers identified in this study (e.g., resistance to hospitals, transportation). The vast diversity of ethnicities in the Brazilian Amazon will be a challenge, and additional studies should be conducted regarding preparing HCPs to work in intercultural contexts.

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With the advancements in therapeutics and available treatment options, almost all deaths and permanent disabilities from snakebite envenoming (SBE) are preventable. The challenge lies in implementing these evidence-based treatments and practices across different settings and populations. This study aims to compare data on provider perceptions of SBE care across health systems and cultural contexts to inform potential implementation science approaches. We hypothesize different health systems and cultural contexts will influence specific perceived needs to provide adequate snakebite care within central tenets of care delivery (e.g., cost, access, human resources). We previously conducted exploratory descriptive studies in the US and Brazil in order to understand the experience, knowledge, and perceptions of health professionals treating SBE. In the US, in-depth interviews were performed with emergency physicians from January 2020 to March 2020. In BR, focus group discussions were conducted with health professionals from community health centers at the end of June 2021. The focus group discussions (BR) were originally analyzed through an inductive thematic analysis approach. We conducted a secondary qualitative analysis in which this codebook was then applied to the interviews (US) in a deductive content analysis. The analysis concluded in August 2022. Brazil participants were physicians (n=5) or nurses (n=20) from three municipalities in the State of Amazonas with an average of three years of professional experience. US participants were emergency physicians (n=16) with an average of 15 years of professional experience. Four main themes emerged: 1) barriers to adequate care on the patient and/or community side and 2) on the health system side, 3) perceived considerations for how to address SBE, and 4) identified needs for improving care. There were 25 subthemes within the four themes. These subthemes were largely the same across the Brazil and US data, but the rationale and content within each shared subtheme varied significantly. For example, the subtheme "role of health professionals in improving care" extended across Brazil and the US. Brazil emphasized the need for task-shifting and -sharing amongst health care disciplines, whereas the US suggested specialized approaches geared toward increasing access to toxicologists and other referral resources. Despite similar core barriers to adequate snakebite envenoming care and factors to consider when trying to improve care delivery, health professionals in different health systems and sociocultural contexts identified different needs. Accounting for, and understanding, these differences is crucial to the success of initiatives intended to strengthen snakebite envenoming care. Implementation science efforts, with explicit health professional input, should be applied to develop new and/or adapt existing evidence-based treatments and practices for SBE.

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ABSTRACT Background: Malaria is one of the leading causes of morbidity worldwide, and patient adherence to prescribed antimalarials is essential for effective treatment. Methods: This cross-sectional study, with in-depth telephone interviews, analyzed participants' perceptions of short message service (SMS) in adherence to treatment. Results: Five thematic categories emerged: decreased forgetfulness, the novelty of the tool, easy-to-understand language, the impact of SMS messages during treatment, and suggestions for improvement and complaints. Conclusions: SMS could assist patients in adhering to prescribed antimalarials.

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The COVID-19 pandemic boosted the development of diagnostic tests to meet patient needs and provide accurate, sensitive, and fast disease detection. Despite rapid advancements, limitations related to turnaround time, varying performance metrics due to different sampling sites, illness duration, co-infections, and the need for particular reagents still exist. As an alternative diagnostic test, we present urine analysis through flow-injection-tandem mass spectrometry (FIA-MS/MS) as a powerful approach for COVID-19 diagnosis, targeting the detection of amino acids and acylcarnitines. We adapted a method that is widely used for newborn screening tests on dried blood for urine samples in order to detect metabolites related to COVID-19 infection. We analyzed samples from 246 volunteers with diagnostic confirmation via PCR. Urine samples were self-collected, diluted, and analyzed with a run time of 4 min. A Lasso statistical classifier was built using 75/25% data for training/validation sets and achieved high diagnostic performances: 97/90% sensitivity, 95/100% specificity, and 95/97.2% accuracy. Additionally, we predicted on two withheld sets composed of suspected hospitalized/symptomatic COVID-19-PCR negative patients and patients out of the optimal time-frame collection for PCR diagnosis, with promising results. Altogether, we show that the benchmarked FIA-MS/MS method is promising for COVID-19 screening and diagnosis, and is also potentially useful after the peak viral load has passed.

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BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency testing is not routinely performed before primaquine treatment in most Plasmodium vivax endemic areas, despite the risk of primaquine-associated hemolysis. This is due to the operational challenges associated with pragmatic G6PD testing and as such needs to be addressed. METHODS AND FINDINGS: This mixed-methods operational study was aimed at implementing the quantitative point-of-care StandardTM G6PD (SD Biosensor, Korea) screening test in malaria treatment units (MTUs) in the municipalities of Rio Preto da Eva and Mâncio Lima, in the Brazilian Amazon, between mid-January 2020 and December 2020. In total, 1286 P. vivax cases were treated based on the Standard G6PD test: 1230 had activity equal to or greater than 4.0 U/g Hb, and 56 less than 4.0 U/g Hb. No G6PD deficient (G6PDd) genotypes were found in 96 samples from the 1230, and only 21 of the 56 G6PDd cases had confirmed G6PDd genotypes. Evaluations were conducted on the proficiency of health care professionals (HCPs) training to perform the test, the reliability of testing performed in the field, and the perceptions of HCPs and patients about the implementation. Post-training proficiency was 73.4% after a 4-hour training session. This study revealed that locations with lower malaria caseloads will need regular refresher training. The test was well accepted by both HCPs and patients. Signs and symptoms of hemolysis were not always associated with malaria treatment drugs by HCPs and patients. INTERPRETATION: Point-of-care quantitative G6PD testing can be performed at MTUs in the Brazilian Amazon to inform treatment decisions with primaquine. Limitations related to technical and cultural aspects need to be addressed further when expanding screening to larger areas.

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The fragmentation chemistry of the protonated and ionized nanoPutian 1 has been studied in the gas phase via electrospray ionization and tandem mass spectrometry. A direct analogy was observed between the fragmentation chemistry of this fascinating "humanoid molecule" and "cleavages" at certain parts of the human body. We argue that such direct analogy and illustrative schemes for the fragmentation of molecular ions of 1 offer a ludic and efficient tool to teach and capture attention to ion chemistry in mass spectrometry. Using the changes in mass for the two heavier nanoPutians with different head styles but the same body design, the analogy has also been used to predict mass spectra. The concepts of isotopic labelling and dissociation thresholds have also been illustrated. For many years, the approach has been successfully used by one of us in classes and lectures, mainly when presenting ion chemistry to students and audiences from fields other than Chemistry, most particularly from Biology, Medicine, and Forensic Chemistry.

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Snakebite envenoming (SBE) is a neglected tropical disease with significant global morbidity and mortality. Even when antivenom is available in low-resource areas, health workers do not receive adequate training to manage SBEs. This study aims to develop and validate a clinical practice guideline (CPG) for SBE management across Brazil. A panel of expert judges with academic and/or technical expertise in SBE management performed content validation. The content validity index (CVI) score was 90% for CPG objectives, 89% for structure and presentation and 92% for relevance and classified the CPG as valid. A semantic validation was performed by analyzing focus group discussions with doctors and nurses from three municipalities of the Brazilian Amazon, after a 5-day meeting during which the CPG was presented. Two central themes emerged: knowledge acquired during the meeting and recommendations for improving the CPG. Based on these results, the CPG was revised into a final version. This study presents the successful development and validation process of a CPG for SBE management, which is targeted to a specific low-resource, high-burden setting. This development and validation process can be adapted to other settings and/or other neglected tropical diseases.

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